Epigenetic Regulation of Muscle Differentiation by the Chromatin Remodeling Protein ING2

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Chromatin remodeling is an epigenetic mechanism that controls cell proliferation and differentiation, which are fundamental in the developing and adult individual. A major focus of my research program is to understand how chromatin remodeling contributes to cell differentiation. Using muscle cell differentiation (or myogenesis) as a model, we have found that the chromatin remodeling protein ING2 promotes muscle differentiation. Our data suggest that ING2 may cooperate with the Brg1-SW/SNF chromatin remodeling multiprotein complex to positively regulate cell differentiation. We have confirmed that ING2 is a target of sumoylation, where a SUMO molecule is attached reversibly to ING2. Our preliminary data suggest that ING2 might be sumoylated in muscle cells to suppress the ability of ING2 to promote muscle differentiation.  Thus, we hypothesize that the interaction of ING2 with the Brg1-SWI/SNF multiprotein complex leads to activation of myogenin, which is the master regulator of muscle differentiation, and that sumoylation negatively affects ING2 promotion of myogenin expression and hence muscle differentiation. ******We will determine the ability of ING2 to interact with the Brg1 complex, specifically on promoter of the myogenin gene in the myogenic C2C12 cells during muscle differentiation. We will also determine if the interaction between ING2 and the Brg1-SWI/SNF complex is important for muscle differentiation. Moreover, we will determine the role of sumoylation in regulating ING2 function in differentiation using SUMO loss of function and gain of function approaches. Taken together, we will understand ING2 functionality and the role of chromatin remodeling in muscle and cell differentiation in general. **